Effects of isoflurane, sevoflurane, propofol and alfaxalone on brain metabolism in dogs assessed by proton magnetic resonance spectroscopy (1H MRS)

Abstract

Background: The purpose of this study was to determine the effects of isoflurane, sevoflurane, propofol and alfaxalone on the canine brain metabolite bioprofile, measured with single voxel short echo time proton magnetic resonance spectroscopy at 3 Tesla. Ten adult healthy Beagle dogs were assigned to receive isoflurane, sevoflurane, propofol and alfaxalone at 3 different dose rates each in a randomized cross-over study design. Doses for isoflurane, sevoflurane, propofol and alfaxalone were F_E'Iso 1.7 vol%, 2.1 vol%, 2.8 vol%, F_E'Sevo 2.8 vol%, 3.5 vol% and 4.7 vol%, 30, 45 and 60 mg kg^{- 1} h^{- 1} and 10, 15 and 20 mg kg^{- 1} h^{- 1} respectively. A single voxel Point Resolved Spectroscopy Sequence was performed on a 3 T MRI scanner in three brain regions (basal ganglia, parietal and occipital lobes). Spectral data were analyzed with LCModel. Concentration of total N-acetylaspartate (tNAA), choline, creatine, inositol and glutamine and glutamate complex (Glx) relative to water content was obtained. Plasma concentration of lactate, glucose, triglycerides, propofol and alfaxalone were determined. Statistics were performed using repeated measures ANOVA or Wilcoxon Sign Rank test with alpha = 5%.

Results: Plasma glucose increased with isoflurane, sevoflurane and alfaxalone but decreased with propofol. Plasma lactate increased with all anesthetics (isoflurane > sevoflurane > propofol > alfaxalone). Cerebral lactate could not be detected. Only minor changes in cerebral metabolite concentrations of tNAA, choline, inositol, creatine and Glx occurred with anesthetic dose changes.

Conclusion: The metabolomic profile detected with proton magnetic resonance spectroscopy at 3 Tesla of canine brain showed only minor differences between doses and anesthetics related to tNAA, choline, creatine, inositol and Glx.

Keywords: Anesthesia; Canine; Cerebral; Glucose; Lactate; LcModel; MRI; PRESS; Plasma.

Fig. 1

Schematic timeline for propofol and alfaxalone (a) and isoflurane and sevoflurane (b) The 30 min equilibration phase was followed by a measurement period of approximately 30 min where a total of three measurements were performed (BG, PL and OL). For treatment I and S the end expiratory concentration had to be adjusted before each equilibration phase. Jugular venous blood samples were taken for serum glucose, lactate and plasma concentrations of propofol and alfaxalone

Fig. 2

T2 weighted images of the brain of one beagle dog. Transversal (left), dorsal (middle), parasagittal (right; a and b) or sagittal (right; c) view; The red rectangles display the ¹H MRS voxels of interests (VOI) for left basal ganglia (a), left parietal lobe (b) and midline occipital lobe (c)

Fig. 3

Example ¹HMRS spectra of basal ganglia (a) parietal lobe (b) and occipital lobe (c) in one dog receiving 1.5 MAC (2.1 vol%) isoflurane. The x-axis represents the chemical shift in ppm of each metabolite and the y-axis represents the signal intensity

Fig. 4

Plasma concentration of propofol and alfaxalone in mg L^− 1 for doses 1, 2 and 3. First and third quartiles are defined by the boxes and the median by the band inside. Minimum and maximum is indicated by the whiskers. * Significant difference to dose 2 and 3 (p < 0.05)